6-5109358-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020408.6(LYRM4):c.*65A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 1,606,436 control chromosomes in the GnomAD database, including 206,424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (16531 hom., cov: 32)
  • Exomes 𝑓: 0.50 (189893 hom.)
• Consequence: LYRM4 NM_020408.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.84

Genes affected

LYRM4 (HGNC:21365): (LYR motif containing 4) The protein encoded by this gene is found in both mitochondria and the nucleus, where it binds cysteine desulfurase and helps free inorganic sulfur for Fe/S clusters. Disruption of this gene negatively impacts mitochondrial and cytosolic iron homeostasis. [provided by RefSeq, Sep 2016]

LYRM4-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-5109358-T-G is Benign according to our data. Variant chr6-5109358-T-G is described in ClinVar as [Benign]. Clinvar id is 1294407.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYRM4	NM_020408.6	c.*65A>C		3_prime_UTR_variant	3/3	ENST00000330636.9
LYRM4-AS1	NR_126015.1	n.373+36624T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYRM4	ENST00000330636.9	c.*65A>C		3_prime_UTR_variant	3/3	1	NM_020408.6	P1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65989 AN: 151892 Hom.: 16525 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.435

GnomAD4 exome AF: 0.504 AC: 733754 AN: 1454426 Hom.: 189893 Cov.: 41 AF XY: 0.504 AC XY: 364333 AN XY: 722202

Gnomad4 AFR exome AF: 0.175

Gnomad4 AMR exome AF: 0.508

Gnomad4 ASJ exome AF: 0.486

Gnomad4 EAS exome AF: 0.793

Gnomad4 SAS exome AF: 0.458

Gnomad4 FIN exome AF: 0.610

Gnomad4 NFE exome AF: 0.503

Gnomad4 OTH exome AF: 0.503

GnomAD4 genome AF: 0.434 AC: 66007 AN: 152010 Hom.: 16531 Cov.: 32 AF XY: 0.443 AC XY: 32929 AN XY: 74290

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.805

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.512

Gnomad4 OTH AF: 0.439

Alfa AF: 0.474 Hom.: 16319

Bravo AF: 0.414

Asia WGS AF: 0.562 AC: 1954 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.3
Dann	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9606; hg19: chr6-5109592;